Novel n-(3,5-dihalophenyl)-imide compounds

ABSTRACT

NOVEL N-(3,5-DIHOLOPHENYL)IMIDE COMPOUNDS, WHICH EXHIBIT A STRONG ANTIMICROBIAL ACTIVITY AGAINST MICROORGANISMS INCLUDING PHYTOPATHOGENIC FUNGI, PARASITES OF INDUSTRIAL PRODUCTS AND PATHOGENIC MICROORGANISMS, REPRESENTED BY THE FORMULA,   (3-X,5-X&#39;&#39;-PHENYL)-N&lt;(-CO-A-CO-)   WHEREIN X AND X&#39;&#39; EACH REPRESENT HALOGENS AND A REPRESENTS A SUBSTITUTED ETHYLENE SUCH AS CHLOROETHYLENE, C1C4 ALKYLTHIOETHYLENE, C1-C2 ALKYL-ETHYLENE OR 1,2-DI-C1C2-ALKYL-ETHYLENE, A CYCLOPROPYLENE SUCH AS 1,3-DIMETHYLCYCLOPROPYLENE, TRIMETHYLENE, A CYCLOHEXYLENE-1,2-, CYCLOHEXENYLENE-1,2-, CYCLOHEXADIENYLENE-1,2- OR O-PHENYLENE. THE N-(3,5-DIHALOPHENY)IMIDE COMPOUNDS CAN BE OBTAINED BY ANY OF METHODS WHICH PRODUCE IMIDE COMPOUNDS ON REACTION OF AN N-(3,5-DIHALOPHENYL)MALEIMIDE COMPOUND WITH A MERCAPTAN, A HYDROGEN HALIDE, PHOSPHORUS CHLORIDE OR THIONYLCHLORIDE.

United States Patent US. Cl. 260-326.5 S 6 Claims ABSTRACT OF THEDISCLOSURE Novel N-(3,5-dihalophenyl)imide compounds, which exhibit astrong antimicrobial activity against microorganisms includingphytopathogenic fungi, parasites of industrial products and pathogenicmicroorganisms, represented by the formula,

wherein X and X each represent halogens and A represents a substitutedethylene such as chloroethylene, C C alkylthioethylene, C -Calkyl-ethylene or l,2-di-C c -alkyl-ethylene, a cyclopropylene such as1,3-dimethylcyclopropylene, trimethylene, a cyclohexylene-1,2-,cyclohexenylene-1,2-, cyclohexadienylene-1,2- or o-phenylene.

The N-(3,5-dihalophenyl)imide compounds can be obtained by any ofmethods which produce imide compounds or reaction of anN-(3,5-dihalophenyl)maleimide compound with a mercaptan, a hydrogenhalide, phosphorus chloride or thionylchloride.

The present invention relates to novel N-(3,5-dihalophenyl)imidecompounds and their production and use.

The said N-(3,5-dihalophenyl)imide compounds are represented by theformula,

3,745,170 Patented July 10, 1973 wherein X and X represent halogenatoms, and A represents a substituted ethylene group of the formula,

wherein R is alkyl of 1-4 carbon atoms, halogen, alkylthio of l-10carbon atoms, lower alkenylthio, lower acylthio, aralkylthio,phenylthio, halogenated phenylthio, methylated phenylthio, nitratedphenylthio, dialkylamino (the alkyl group has 1-6 carbon atoms), cyclicsecondary amino of 4-5 carbon atoms, morpholino, alkylsulfinyl of 1-10carbon atoms or aralkylsulfinyl, and R is hydrogen, alkyl of 1-4 carbonatoms or halogen, provided that R is alkyl if R is alkyl, R is halogenif R is halogen, and R is other than alkyl if R is hydrogen, or A represents a cyclopropylene group represented by the formula,

wherein R R R and R each represents hydrogen or alkyl of 1-4 carbonatoms, or A represents trimethylene, cyc1ol1exylene-1,2-,cyclohexenylene-1,2-, cyclohexadienylene-l,2-, or o-phenylene.

In the present invention, examples of the halogen atom include chlorine,bromine, iodine and fluorine, and examples of the cyclic secondary aminogroup include pyrrolidino and piperidino.

It has now been found that the said N-(3,5-dihalophenyl)imide compoundsof the Formula I exhibit a strong anti-microbial activity against a widevariety of microorganisms including phytopathogenic fungi and parasitesof industrial products, and some of them further possess stronganti-microbial activity against pathogenic microorganisms. This findingis unexpectable and surprising because compounds analogous thereto suchas the corresponding 3,5-unhalogenated derivative show no appreciableanti-microbial activity. In this connection, it may be noted that someof such analogous compounds exert a strong herbicidal activity, whereasthe compounds of the present invention have no herbicidal action.

A fundamental object of the present invention is to provide the novelN-(3,5-dihalophenyl)imide Compounds I having a marked anti-microbialactivity.

Another object of the invention is to provide a process for preparingthe N-(3,5-dihalophenyl)imide Compounds I.

Other objects will become apparent from the following description.

In accordance with the present invention, the N-(3,5- dihalophenyl)imideCompounds I are prepared according to any of the procedures representedby the equations shown below.

PROCEDURE 1 5 In the case where, in the aforesaid Formula I, A is otherthan an alkylsulfinyl ethylene or aralkylsulfinyl ethylene group, i.e. Ris other than an alkylsulfinyl or In the case where, in the Formula I, Ais a substituted eth'ylene group, in which R is hydrogen and R isalkylthio, lower alkenylthio, lower acylthio, aralkylthio, halogenatedphenylthio, methylated phenylthio, nitrated phenylthio, dialkylamino,cyclic secondary amino, morpholino or halogen:

(IV) (Ib) PROCEDURE 3 In the case where, in the Formula I, A is asubstituted ethylene group, in which R is hydrogen and R is chlonne:

NH( -CH=GH-O-OH PC1 01 SO01, t

, /JJCH--Cl N l A PROCEDURE 4 In the case where, in the Formula I, A isa substituted ethylene group, in which R; is hydrogen and R isalkylsulfinyl or aralkylsulfinyl:

In the above-mentioned formulas of the procedures 14, X and X are asdefined previously, A is a substituted ethylene group represented by theformula,

wherein R is as defined previously, and R is alkyl of 1-4 carbon atoms,halogen, alkylthio of 1-10 carbon atoms, lower alkenylthio, loweracylthio, aralkylthio, phenylthio, halogenated phenylthio, methylatedphenylthio, nitrated phenylthio, dialkylamino (the alkyl group has 1-6carbon atoms), cyclic secondary amino of 4-5 carbon atoms or morpholino,provided that R is alkyl if R is alkyl, R is halogen if R: is halogenand R is other than alkyl if R, is hydrogen, or a cyclopropylene grouprepresented by the formula,

wherein R R R and R, are as defined previously, or trimethylene,cyclohexylene-1,2-, cyclohexenylene-1,2-, cyclohexadienylene-1,2- oro-phenylene; R is alkylthio of 1-10 carbon atoms, lower alkenylthio,lower acylthio, aralkylthio, phenylthio, halogenated phenylthio,diakylamino (the alkyl group has 1-6 carbon atoms), cyclic secondaryamino of 4-5 carbon atoms, morpholino or halogen; :R' is alkyl of 1-10carbon atoms, aralkyl or lower alkenyl.

On the basis of each of the above-mentioned procegures, the process ofthe present invention is explained elow.

PROCEDURE 1 This procedure is due to the dehydration reaction of amono-N-(3,5-diha1ophenyl)amide of dicarboxylic acid Compound H.According to this procedure, all the N- (3,5-dihalophenyl)imidecompounds of the present invention can be synthesized, except the casewhere A in the Formula I is alkylsulfinyl ethylene or aralkylsulfinylethylene. When this procedure is adopted, the desired N-(3,5-dihalophenyl)-imide Compounds Ia can be easily prepared by merelyheating the mono-N-(3,5-dihalophenyl) amide of dicarboxylic acidCompound II to 150-250 C., preferably l80-200 C., or by bringing thesaid Compound II into contact with a suitable dehydrating agent at20-150 C., preferably 60-l00 C. Examples of the dehydrating agentinclude acid anhydrides such as acetic anhydride, phosphoruspentachloride, phosphorus oxychloride, phosphorus pentoxide, acetylchloride and thionyl chloride, but particularly preferable dehydratingagent is acetic anhydride. The amount of the dehydrating agent is morethan an equimolar amount of the Compound H. The dehydration reactionproceeds even in the absence of a reaction medium, but is preferablyeifected in the presence of a heating medium or a solvent. Examples ofthe heating medium include xylene, liquid paraflin, nit-robenzene,dichlorobenzene, etc., and examples of the solvent include benzene,toluene, xylene, chloroform, carbon tetrachloride, etc. The reactionterminates in a period of 30 minutes to hours, in general.

In the case where, in the Formula H, X is identical with X' and thegroup A is not symmetric, there are two kinds of plane structure isomersas the starting mono- N-(3,5-dihalophenyl)amide of dicarboxylic acidCompound II. No matter which starting material is used, however, theresulting N-(3,5-dihalophenyl)imide Compound Ia is same in structure.

The mono-N-(3,5-dihalophenyl)amide of dicarboxylic acid Compounds 11,which are used as the starting materials in this procedure, are novelcompounds and are easily obtainable by reacting, for example, acorresponding 3,5-dihaloaniline with a corresponding acid anhydride, asshown in the following equation:

NH, o A

x v11 A VIII 2 Q-NH-E-N-i-OH PROCEDURE 2 This procedure is due to theaddition reaction of N- (3,5-dihalophenyl)maleimide Compounds III tocarboncarbon double bonds. The said addition reaction is accomplished bymerely bringing the N-(3,5-dihalophenyl)- maleimide Compound IH intocontact with an equimolar amount or slight excess of a compoundrepresented by the Formula IV. The reaction temperature varies dependingon the kind of R but, in general, is 10 to 100 C., preferably 0 to 30C., in case R is alkylthio, lower alkenylthio, lower acylthio,aralkylthio, phenylthio, halogenated phenylthio, methylated phenylthio,nitrated phenylthio, dialkylamino, cyclic secondary amino of 4-5 carbonatoms or morpholino, and is 0 to 100 C., preferably 20 to 50 C., in caseR is halogen. The abovementioned reaction is preferably effected in asolvent. The kind of the solvent used varies depending on the kind of RGenerally, however, the solvent is selected from benzene, toluene,xylene, aliphatic hydrocarbon, solvents weak in polarity such as ether,chloroform, etc., dioxane, tetrahydrofuran, dimethylformamide,dimethylsulfoxide and the like. Further, in case R is other thanhalogen, a suitable basic catalyst is used. Whereby the reactionprogresses easily. Examples of the basic catalyst include tertiaryamines such as t-riethylamine, dimethylaniline, diethylaniline,pyridine, N-methylmorpholine and the like. Particularly, the use oftriethylamine is preferable.

The N-(3,5-dihalophenyl)maleimide Compounds III, which are used as thestarting materials in this procedure, are easily obtained by reacting,for example, a corresponding 3,5-dihaloaniline with maleic anhydride(refer to Dutch patent application No. 6817250 filed by SumitomoChemical Co.).

PROCEDURE 3 This procedure is due to the reaction ofN-(3,5-dihalophenyl)maleamic acid Compounds V with a chlorinating agent.The said reaction is effected by bringing the N-(3,5-dihalophenyl)maleamic acid compound into contact with an equimolaramount or slight excess of phosphorous pentachloride or thionyl chlorideat 0 to 0., preferably 20 to 80 C. If necessary, the reaction is carriedout in a suitable solvent. Examples of the solvent include chloroform,carbon tetrachloride, chlorobenzene, etc.

After completion of the reaction, the reaction product is washed withwater, dried and then recrystallized from a suitable solvent such as,for example, benzene-ethanol, petroleum benzin-benzene, ligroin-benzeneor n-hexanebenzene, whereby the desired product can be easily obtained.

The N-(3,5-dihalophenyl)maleamic acid Compounds V, which are used as thestarting materials in this procedure, are readily obtainable byreacting, for example, a corresponding 3,5-dihaloaniline with maleicanhydride.

PROCEDURE 4 This procedure is due to the oxidation reaction of thioetherCompounds VI. The oxidation reaction is easily accomplished by bringingthe thioether Compound VI into contact with at least a stoichiometricamount of a suitable oxidizing agent such as, for example, hydrogenperoxide, an organic peracid, i.e. performic, peracetic or perbenzoicacid, chromic acid or permanganate, at 0 to 40 0., preferably 20 to 30C. In the case of employment of chromic acid or permanganate, it isdesirable that the oxidizing agent is not used in large excess. Thereaction is desirably effected in a solvent. Examples of the solventinclude water and water-miscible solvents such as acetone, alcohol,acetic acid and the like. The thioether Compounds VI, which are used asthe starting materials in this procedure, are obtained according to theaforesaid procedure 1 or 2. v

The N-(3,5-dihalophenyl)imide Compounds I obtained in the above mannerare purified, if necessary, by a suitable means, e.g. byrecrystallization from a proper solvent.

As mentioned previously, the N-(3,5-dihalophenyl)- imide Compounds I ofthe present invention exert a strong anti-microbial activity againstvarious microorganisms including phytopathogenic fungi (e.g. Pyriculan'aoryzae, Cochliobolus miyabeanus, Xanthomonas oryzae, Sphae rothecafulginea, Pellicularza sasakii, Pellicularia filamentosa, Fusariumoxysporum, Corticium rolfsii, Botrytis cinerea, Sclerotina sclerotiorum,Alternaria kikuchiana, Alternaria mali, Glomeralla cingulata, andPythium aphanidermatum) and parasites of industrial products (e.g.Aspergillus niger) and pathogenic microorganisms (e.g. Staphylococcusaureus, Escherichia coli, Tri- 8 TEST 1 Each of the test compounds inthe form of wettable powders was diluted with water to a givenconcentration and sprayed to rice plants, which had been cultured inchophyton rubrum). 5

Further, the characteristic physiological activity of ptots 9 m z a z 3have: the present compounds is observed only in the case where lif :3 ggi g g i g g g; gg g z i Z P g been g g f the with a spore suspension ofPyricularia oryzae. 5 days trogen o t e e compoun an not 0 1Othereafter, the number of diseased spots was counted. Served at an m thecase where other Phenyl groups have The results were as shown in thetables below, from which been substituted therein. In order tosubstantiate this and it is understood that the N(3,5-diha1Opheny1)imide the fat that the Pmstint compounds have $11011Stmng and pounds I are stronger in anti-fungal activity (against Ricebroad microbicidal effects as not seen in microbicides blast) thancompounds analogous thereto such as the corof the prior art, typicaltest results are set forth below. responding other isomeric compounds.

TABLE 1 No. of diseased Concenspots ration er 10 No Compound (p.p.m.)eaves I C-OH-S 0H=(0H,)=0H, 5} I G-CH: 1 Ii C] II o-0H-s--o1 I I CCH, 01

C-CH-N a \C-- H:

Br II QR l C- H: Br 3 Reference compound (f-CH;

Untrea TABLE 2 No. of Concendiseased tration spots per No. Compound(p.p.m.) 10 leaves 1 (I) 1,000 38 C\ 01 -C I Cl II 0 6 2..---- El) 1,000

C\ C1 H -C l 0 Cl Reference compound 3..---- fl) 1, 000 312 C II 0Reference compound 4".-. E 1,000 264 E Cl Reference compound 5----- E1,000 28 C HI 8 Untreated 285 TABLE 3 N0. of Concendiseased trationspots per No. Compound (p.p.m.) leaves 1.-..- O 500 2.8

J5 1 CHg-Cfi \N CHa( JH Br CH;--CH \N Ulla-( J5 Reference compound 3"...E 500 30.7

CH3 ?H CHa-CH Untreated 38. 9

TABLE 4 No. of Concendiseased tration spots per No. Compound (p.p.m.)leaf a Cl Cl-CH- /N GHQ-C H 01 Br-CH-C /N GHQ-C H Br C1-CH-C /N CHz-C IBr Reference compound C1-CH- Q Hr-C A Reference compound Cl-CH-ii\ CHa-C('5 Reference compound C1--CH- /N CHg-C TABLE 5 No. of Concem diseasedtration spots per No. Compound (p.p.m.) leaf -CH- S O CHICH;

C-CH: 1 4') Untreated 4 3 8 TEST 2 Each of the test compounds in theform of dusts was applied to rice plants, which had been cultured inpots of 9 cm. in diameter and grown up to the 4 leaves stage, in aproportion of mg. of the dust per pot by use of a duster. After one day,the plants were inoculated by spraying with a spore suspension ofCochliobolus miyabeanus. 3 days thereafter, the number of diseased spotswas counted. The results were as shown in the tables below, from whichit is understood that the N-(3,5-diha1ophenyl)imide Compounds I arestronger in anti-fungal activity (against Helminthosporium leaf spot ofrice) iug other isomeric compounds.

than compounds analogous thereto such as the COIICSPOlldr TABLE 6 No. 01Coneendiseased tration spots per No. Compound (p.p.m.) lea! -GH-S-CH CH2 Cl 0 500 O /gOH-S-CH:(OH|):CH; i

C-- H Ci 3 C- E l )i-cn-som-Q C- H: l

6..:r.-::.. cl CH|CH 500 19 3-CHN -N\ CHgCH;

C- H C! CH-N N\ w -OH-N b \C H] l C- H: B: ll

Refemnoe compound 14 TABLE 8C0ntinued TABLE 7 Compound No. of

Concendiseased tration spots per (p.p.m.) leaf Compound d m R m n U 0 20 L 0 w 0| M 1 N 0 0 H C C C C w H u u 3 m 1. mm m 1 m p mu 2 WWW um C 19 E L l 1 m c C T N d m 0 0 C 0 0 p m G o C m n N L 0 5 3 3 M 1 m c m mm N N J LL; film m m 4% 5 m 0 ml r 0" 0H 0 C 0 0 2" L m m am cm W m m mm r I I m N N o c c o n c c c n H H H Una-safari m C C m w w n N m H m0" C" H u n 5 w m H mm 0 map 8?. NM M mu 2 Wm n e o m c m 8 E m 1 m A 0!I T N d "fl w H H m C 2 C 0 /H\ C C u m n N L TABLE 9'Cont1nued TABLE10'Continued No. of No. of Concendtseevsed Concendlfsewsed oration spotsper -t1ratfon spots per No Compound (percent) leaf No. Compound(percent) l'eaf e-.--. H 2 78.1 5 s--. o 2.0 68.4

g CH:CH--

\@ L CH: H-C .5 0 Reference compound Reference compound 6. 3 l 2. 0 56.2 7. 0 2 59. 8 CH -CH- CH;- H-C 0 Cl Reference compound 3 7...... O 2 000. 1

Reference compound CHr-CH- 01 s..... o 2 13.2

) OH.- HC

Unmmm 3 \C HI Reference compound 0 4 T ABLE u e..... 0 2 7 No. of &Coneendiseased tmtfon spo \N N 0. Compound (percent) per leaf Q 1 0 Cl10 0 C CHI-g a I Untreat 76. 9 C H:|G 1

TABLE 10 No. of 2...... Br 0 2.0 0. 8 Concendiseased ll: 01

tratfon spots 0H- No. Compound (percent) per leaf \N 1...... CHI 0 2.0 0Hg-O CH 01 g l N H-0 8...... Cl 0 2. 0 2. 4 g 1 a Cl C 1 CH- 2.-.-- CHI0 B 2.0 0.9 C H-O r C 4.....- Of 0 2. 0 1. 1

g B! 8...... 0 I 2. 0 1. 8 311-.

CH -G H l N /N Ha-(fi t CH;- H-(fi I 0 0 20 0.3 B O 2.0 1.9 a 01 5 g ofCHg-CH- GH- N N 0 H H-0 H-0 Reference compound Reference compound 18TABLE 11-Con-tinued 17 TABLE 11Con*tin'ued Concendiseased tration spotsper (percent) l'eaf No. Compound Concendiseased tiration spots per(percent) 'leaf No. Compound d m m. m c m m C 0 C 0 m H H C C l\ C m 0 2M o 2 ml i J H H C -C l\ O u n 7 Reference compound 4. e 1 e3 mm l m.mmum u 9 w m f od mm .mam m e mmmm M 3 .m fiO I! m T P m m Pmnm m P wflwuu t n Mmaw who 5 6 WW m sm m pm ft 3 H m C qwfl a t E m mm wma 5 3 2 3 5o 2 d m o p m m N m m i 4 m H H C C 40 portion of 10 ml. of the dilutionper pot. After 3 hours,

TABLE 12 I s mwmm 08p Nm u m D mmm nae

mun m E if C-CH-S OGH:(CH2) 2CH;

19 a mycelium-disc-inoculurn of Pellicularia sasakiz' was applied ontothe sheaths. 5 days thereafter, the infectious state of the sheaths wasobserved, and the degree of damage was calculated according to thefollowin equation:

(infection number of index stems Total number of stems 3 wherein theinfection index was determined on the basis of the following criteria:

Degree of damage= X 100 The results were as shown in the tables below,from which it is understood that the N-(3,5-dihalophenyl)imide Compounds1 are stronger in anti-fungal activity against 10 Sheath blight of ricethan compounds analogous thereto.

TABLE 13 Concen- Degree No. Compound ($332? damage -CH-S-OHa-CH; G 1

CCHi I (-CH-S-CHKCHMGH;

l CCHa ii-orr-s-Q Q I E-CH:

4 u:- 0 200 1.8 ii-cn-s-Q-cl N (fiCH:

6 O 200 3. 9 -CH-S CHI-Q Q ECH C-CH-N I b GCH c-cH-s-Q N CCH:

Reference compound (Lon-SQ Q l CCH:

Q 'IUZ 200 8. 6

Untranfnrl 100 carbamate.

23 24 TABLE 17-Continued TEST 4 o dis e s spots er Farm soil was chargedinto pots of 9 cm. in diameter, cmlpmnd and a soil (10 ml.) infectedwith Pellicularia filamentosa H 01 5 was dispersed over the surface ofsaid soil. Each of the ClCH-0 I test compounds in the form ofemulsifiable concentrates I N- was diluted with water to a givenconcentration, and the ()I-OH-C/ dilution was applied into each pot in aproportion of O1 10 ml. per pot. After 2 hours, 10 seeds of cucumberwere Reference compound sowed therein. 5 days thereafter, the infectiousstate of the e 500 100 grown seedlings was observed, and the percentageof stand C1OHG\ was calculated according to the following equation:

CHr-

u, Percentage of stand Reference compound Number of healthy seedlings intreated plot X 100 7-. 0 500 100 Number of germinated seedlings in IIuntreated and uninoeulated plot C1-CH-C\ I CHr-O 0H The results were asshown in the tables below, from s Reference compoundTUZ 500 3.7 which itiS understood that the N-(3,5-dihalophenyl)- Untreated TABLE 18 Concen-Degree tration of No Compound (p.p.m.) damage /C-OH-SOCH:OHI QK L C- H101 ll 0 C-=-CE--SOGH2(CH2)2CH1 0- H1 01 ll /C-OHSOCH2 C- H: 1 H

L.:::::: Reference compound TUZ.::::::::::::::: 600 3. 8

Untreated 10 imide Compounds I are stronger in soil disinfectantactivity than compound analogous thereto.

TABLE 19 Concentration Percentage No: Compound (p.p.m.) of stand/GCH--S-CH:CHI

C-CH; 1 ll TABLE 19-Contfnued Coneen- Degree tration of No. Compound(p.p.m.) damage G1 I! I /CCHS Cl C- H: l

CH-S--CH: N\ l a 0- H2 5...: .2: O CHICK! 500 78. 8

-CH-N N\ GHzCH:

C- H; 1 II -Q N\ L C- H: r ll Untreated (inoculated)- o Untreated(uninoeulated) 100 TABLE TABLE 21 Concen- Concentration Percentagetration Percentage No. Compound (p-p-m) stand No. Compound (p.p.m.)ofstand ll r r e g 01 CH-C CH2- H:C\ N- 6 /N r C N 0110 H CHC H: /N

1 5 cm-c g B: 3..... CH 0 1,000 90.1

I Reference compound CH2&\ Reference compound OH, 4..." E 1,000 0 \CHr IE Reference compound Reference com ound' Q1 1 50 me 5--." p 1,000 93:7 4

01 NO c1 -N0,

1 C1 C1 0 l Untreated (moculatemfln Untreated(1n0eu1ated)..-.:::::=:-.-.=::::m:= 0 Untreated (unfnoculated). 100. 0Untreated (unlnoouleted)-::::::::::::::::;:=:; 100

'Fungioide used as soil disinfectant.

Fungiolde used as soil dllinfectant.

27 TABLE '23-Continued TABLE 22 No. of Colleen tration Percentage Egg;gj gg No; Compound of Stand N0. Compound (p.).m.) leaf f 500 8 Referencecompound 5--.: 01 01 500 as. e

01- -No, F C1 ('31 1 A Untreated (inoculated)....-----w 0 2- Same asabove-::::::::=;.::.=r 500 87. 3 Untreated (uninoculatedh 100 3-...-- 9500 90.2

f H N TABLE 24 Concentration Percentage f 1 No; Compound (D-P-m.) ofstand 0 1.... 01 o 500 98.5

Reference compound i 4.-.: (I) 500 0 l ll Br (I) CH-C A Referencecompound Hrc I Br 5-..: C1 C1 500 80.4

".2 B1 500 91. 2 01 --NO: ll 01 CH-O C! 1 I Untreated(inoculated)..-.:::::::::::::::::=::= 0 H. Untreated(uninoculated)-::::::::::::::::::= 100 13 y 1 Reference compound g CiTABLE 23 I Concen- I tration Percentage No: Compound (p.p.m.) of stand g1 1...: as; o C1 500 100 C L I Reference compound l Q 5...: c1 o 500 0.8

01 CH Ge. 3 l 2*@ 2...: on, B 500 91.3 E

CH-C Q Reference compound CH-lfi B 6 E 500 o C1-CH-- C 1 O 3...: 0H, 0500 98.4 i

H c! Hz-C CHC\ I g CE I Cl Reference compound 7...: C1 C1 500 96.6 0 H,(k

Reference compound 01- N01 1...: Us; 0 500 0 cH- 1 l I 0 (DH-(T 0o TABLE25 Concentration Percentage No. Compound (p.p.m.) of stand C-CH-S CHzGH:

(E C- H:

C-CH-S O OH2(CH2)BCHI C- H: l I

/C-OHS 0 CH N\ l C- H: 1 ll Reference compound CIQNOA 1 l Untreated(Inoculated) 0 Untreated (Unlnoculated) .nxzzszrn::zznzznrztn: 100

TEST 5 TABLE v h a m r r mm i Degree: Eac of the test compoun s in e orm0 we e ra on o powders was diluted with water to a given concentrationNo compfmnd damage and applied to pumpkin seedlings, which had been cul-& 01 1,000 tured in pots of 12 cm. in diameter and grown up to the 3-4leaves stage, in a proportion of 7 ml. of the dilution per pot. Afterone day, the seedlings were inoculated by spraying with a sporesuspension of Sphaerotheca fulginea. 01 10 days thereafter, theinfectious state of the upper 4 c a ll leaves of the seedlings wasobserved, and the degree of 1.000 41 7 damage was calculated from theinfectious area according to the following equation.

a Degree of damage H-C 2, (infection indexXnumber of leaves) X100 Totalnumber of leaves 5 Untreated s2. 9

wherein the infectious index was determined on the basis of thefollowing criteria: TABLE 21 C Infection index: Infectious area ifi 0None. No.- Compound damage 1 Small. 0 500 2.: 3 Medium. g m 5 Large. I

N The results were as shown in the tables below, from which it isunderstood that the N-(3,5-dihalophenyl)-imc 1 ide Compounds I arestronger in anti-fungal activity (for A powdery mildew) than compoundsanalogous thereto.

32 TABLE 27C0ntlnued TABLE 29 Coneen- Degree Concen- Degree tration oftration of No. Compound (p.p.m.) damage No. Compound (p.p.m.) damage1-.- O1 1,000 0.8 2-.." o 500 0.7 5 II 01 u Br CHC\ N-- CHI-C 3 Cl 0 Br1| 2-.-. 01 0 1,000 2.3 0 g 01 OH- I 3 o 500 14.6

N 01 O Reference compound 0 01 l 3".-. 01\ 1,000 40.2

OBI- Reference compound 4 O 500 45.8

ll Hz-C C /N@ Untrm'mfl 43.3 E Untreated 42.3

TABLE 30 Concentration Degree of N0. Compound (p.p.m.) damage /CCH-SOCHC H; C] l i i.,7.. ---w-. -i .4 i-.. 68.

TABLE 28 TEST 6 C n- De ee f gzf Anti fungal spectrum No Compound(p.p.m.) dam ge By means of the agar dilution method, the growth- 1..;..CH 0 1,000 2.3 inhibiting effects of the N-(3,5-dihalophenyl)imide Com-J f pounds I on various phytopathogenic fungi were investigated. Astypical test results, there are shown in the table N below those ofN-(3',5'-dich1oropheny1)cyclopropanedi- 11-0 1 carboximide. g, A TABLE31 Reference compound M tr mimum concen anon E Test fungi: of inhibition(p.p.m.) Pyricularia oryzae 200 Pellicularia filamentosa 40 Botrytiscinerea 8 g g Sclerotinia sclerotiorum 40 C I Alternaria kikuchiana 40Untm e 50.3 Alternarz'a mali 40 Glomerella cingulata 200 33 TEST 7 Bymeans of a method similar to that as in Test 6, the growth-inhibitingeifects of N-(3',5'-dichlorophenyl)- cyclopropanedicarboximide onAspergillus niger ATCC 9642, which propagates on industrial products,were investigated to obtain the results set forth in the table below.

TABLE 32 Minimum inhibition (p.p.m.)

Compound Cl (DH- I Reference compound Norn.- 2,000 means no activity at2,000 p.p.m.

0 2, 000 CHI- Cal TEST 8 Anti-fungal spectrum By means of the agardilution method, the growthinhibiting effects ofN-(3,5-dichlorophenyl)glutaric acid imide on various phytopathogenicfungi were investigated to obtain the results as set forth in the tablebelow.

TABLE 33 Minimum concentration Test fungi: of inhibition (p.p.m.)Cochliobolus miyabeanus 200 Pellicularia filamentosa 200 Botrytiscinerea 40 Sclerotz'nia sclerotiorum 40 Alternaria kikuchiana 200Alternaria mali 200 TEST 9 Effects of controlling Aspergillus niger ATCC9642 By means of a method similar to that as in Test 8, thegrowth-inhibiting effects of N-(3,5-dichlorophenyl)- glutarimide onAspergillus niger AT CC 9642 were investigated to obtain the results asset forth in the table below.

TABLE 34 Minimum concentration of inhibition (up- Compound NorE.- 5,000"means no activity at 5,000 p.p.m.

TEST 10 Anti-fungal spectrum By means of the agar dilution method, thegrowthinhibiting effects of N (3,5 dichlorophenyl)-a-chloro succinimideon various phytopathogenic fungi were investigated to obtain the resultsas set forth in the following table.

TABLE 35 Minimum concentration Test fungi: of inhibition (p.p.m.)Pyricularia oryzae 200 Pellicularia filamentosa 200 Corticium rolfsii200 Botrytis cinera 200 Sclerotinia sclerotiorum 200 Glomerellacingulata 200 TEST 11 Efifects of controlling Aspargillus niger ATCC9642 By means of a method similar to that as in Test 10, thegrowth-inhibiting eifects of N-(3,5-dichlorophenyl)- a-chlorosuccinimideon Aspergillus niger, which propagates on industrial products, wereinvestigated to obtain the result as set forth in the following table:

TABLE 36 Minimum concentration ofinhi Test compound tion (p.p.m.)

a 01 011- l l /N Ha-C TEST 12 Anti-fungal spectrum By means of the agardilution method, the growthinhibiting eifects ofN-(3,5-dichlorophenyl)-ethylsulfinylsuccinimide (Compound 1) andN-(3,5-dichlorophenyl)- n-butyl-sul'finylsuccinimide (Compound 2) onvarious 35 phytopathogenic bacteria and fungi were investigated toobtain the results as set forth in the following table:

TABLE 37 Minimum concentration of inhibition (p.p.m.)

Com- Com- Test organism pound (1) pound (2) Pyricularia oryzae 200 200Xanthomoms oryzae. 200 200 Pellicularia filamentosa 200 200 P A t u 20o2) Botrytis cinerea 200 40 Sclerotinia sclerotiomm. 200 200 Alternariakz'kuchiana 200 40 Glo'mcrella cingulata 200 40 Cochliobolus miyabeanus200 200 I poriu'm 200 Fusarium pisi 200 Xanthomonas pnmi 200 200 citr200 200 Erwinia aroidae 200 200 TEST 13 Effects of controllingAspergillusniger ATCC 9642 By means of a method similar to that as inTest 12, the growth-inhibiting eflects ofN-(3,5-dich1oropheny1)-ethylsulfinylsuccinimide andN-(3,5-dichlorophenyl)-n-butylsulfinylsuccinimide on Aspergillus nigerATCC 9642 were investigated to obtain the results as set forthin the following table:

| CH SOGHQ(OHI)ROH| As clearly understood from the above description,the N-(3,5-dil1alophenyl)imide Compounds I are useful as anti-microbialagents, particularly as agricultural and industrial and sometimes,pharmaceutical field. In order words, they may be used as agriculturalchemicals for prevention or inhibition of plant diseases caused byphytopathogenic fungi and bacteria. They may be used also as industrialchemicals for preventing or inhibiting industrial products fromstaining.

For the above purpose, the N-(3,5-dihalophenyl)imide Compounds I may beused as they are but, in most practical cases, they are extended with asuitable carrier(s) to bring them into the forms of conventionalfungicides such as dusts, Wettable powders, oil sprays, aerosols,tablets, emulsifiable concentrates, pellets, granules, ointment orpowder. These anti-microbial compositions may contain, in addition tothe N-(3,5-dihalophenyl)imide Compounds I one or more of knownfungicides, insecticides and herbicides such as, for example,Blasticidin S,

Kasugamycin,

Polyoxyn,

Cellocidin,

Chloramphenicol, 0,0-diethyl-S-benzylphosphorothiolate,0-ethyl-S,S-diphenylphosphorodithiolate,

36 On-butyl-S-ethyl-S-benzylphosphorodithiolate,0,0-diisopropyl-S-benzylphosphorothiolate,O-ethyl-S-benzylphenylthiophosphonate, pentachlorobenzaldoxime,pentachlorobenzyl alcohol, pentachloromandelonitrile, pentachlorophenylacetate, iron methylarsonate, ferric ammonium methylarsonate,'y-1,2,3,4,5,6-hexachlorocyclohexane,1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane,0,0-dimethy1-O-(p-nitrophenyl)phosphorothioate, S-[1,2-bis(ethoxycarbonyDethylJ 0,0-dimethyl phosphorodithioate,O-ethyl-O-p-nitrophenyl phenylphosphonothioate, a-naphthylN-methylcarbamate, 0,0-dimethyl-O-(p-nitro-m-methylphenyl)phosphorothioate, 3,4,5,6-tetrahydrophthalimide methyl chrysanthemate,3,4-dimethylphenyl N-methylcarbamate, 0,0-diethyl-O-(2-isopropyl-6-methyl-4-pyrimidinyl) thiophosphate,0,0-dimethyl-2,2-dichlor0vinyl phosphate, 1,1-bis (p-chlorophenyl)-2,2,2-trichloroethanol, 1,2-dibromoethane, 1,2-dibromo-3-chloropropane,zinc ethylene-bis(dithiocarbamate), manganese ethylene-bis(dithiocarbamate) 2,3-dichloro-1,4-naphthoquinone, N-(trichloromethylthio -4-cyclohexene-1,2-dicarb0ximide,N-(1,1,2,2-tetrachloroethylthio)-4-cyclohexcne-1,2-

dicarboximide, 6-methyl-2,3-quinoxaline dithiol cyclic carbonate,tetrachloroisophthalonitrile, sodium p-dimethylaminobenzenediazosulfonate, 2,4-dichloro-6-(2-chloroanilino)-S-triazine,2,4-dichlorophenoxyacetic acid, 4-chloro-2-methylphenoxyacetic acid,3,4-dichloropropionanilide, 2,4-dichlorophenyl-4'-nitrophenyl ether,2-chloro-4,6-bis(ethylamino)-S-triazine, sodium N-(l-naphthyl)phthalamate, etc.

The anti-microbial compositions may also contain one or more ofmaterials known to be active as nematocides, acaricides, fertilizers,soil conditioners, soil disinfectants and plant growth regulators.Examples of typical antimicrobial compositions according to the presentinvention are as follows:

(a) Dusts obtained by dispersing at least one of theN-(3,5-dichlorophenyl)imidc Compounds I as active ingredient to aconcentration of 0.1 to 50% by weight in an inert carrier, e.g. talc,diatomaceous earth, wood flour or clay.

(b) Wettable powders obtained by dispersing at least one of theN-(3,5-dichloropheny1)imide Compounds I as active ingredient to aconcentration of 0.1 to 95%, preferable 0.1 to by weight in an inertadsorbent carrier, e.g. diatomaceous earth, together with a wettingand/or dispersing agent such as an alkali metal salt of a long aliphaticsulfate chain, a partly neutralized sulfuric acid derivative of either apetroleum oil or a natural occurring glyceride or a condensation productof an alkylene oxide with an organic acid.

(c) Emulsifiable concentrates obtained by dispersing at least one of theN-(3,5-dichlorophenyl)imide Compounds I as active ingredient to aconcentration of 0.1 to 50% by weight in an organic solvent, e.g.dimethyl sulfoxide, plus an emulsifier such as an alkali metal salt of along aliphatic sulfate chain, a partly neutralized sulfuric acidderivative of either a petroleum oil or a natural occurring glyceride ora condensation product of an alkylene oxide with an organic acid.

((1) Compositions of the N-(3,5-dichlorophenyl)imidc Compounds Iformulated in the manner commonly employed in the art for thepreparation of microbicidal granules, dusts and aerosols.

Practical and presently-preferred embodiments of the present inventionare illustratively shown below with reference to examples, in whichparts and percentages are by weight.

Examples 1-59 are concerned with the syntheses of the present compounds.

EXAMPLES l-13 Standard operational process for the syntheses of thepresent compounds.

A mixture comprising 0.1 mole of N-(3,5-dihalophenyl) succinamic acid,50 ml. of acetic anhydride and 1 g. of anhydrous sodium acetate is fedto a 100 ml. four-necked flask and is heated with stirring at 100 C. for1 hour. Thereafter, the acetic acid and acetic anhydride are removed bydistillation under reduced pressure, and the residue is washed withwater and dried, whereby a desired N-(3,5-dihalophenyl)succinimide isobtained in a favorable yield. If necessary, recrystallization fromethanol is effected to obtain the desired product in a pure form.

The N-phenylsuccinamic acid employed in the present process is easilyobtainable according to an ordinary procedure from a correspondingsuccinic anhydride derivative and an aniline derivative. Typicalexamples of the succinic anhydride and aniline are as set forth below,but it is needless to say that the scope of the present invention is notlimited thereby.

Succinic anhydrides:

Z-methylthio succinic anhydride 2-ethylthio succinic anhydride2-n-propy1thio succinic anhydride Z-iso-propylthio succinic anhydrideZ-n-butylthio succinic anhydride 2-iso-buty1thio succinic anhydride2-sec-butylthio succinic anhydride Z-tert-butylthio succinic anhydrideZ-n-amylthio succinic anhydride 2-iso-amylthio succinic anhydrideZ-tert-amylthio succinic anhydride 2-hexylthio succinic anhydrideZ-heptylthio succinic anhydride 2-octylthio succinic anhydride2-nonylthio succinic anhydride Z-decylthio succinic anhydride2-phenylthio succinic anhydride 2-(o-chlorophenylth'io) succinicanhydride 2-(m-chlorophenylthio) succinic anhydrideZ-(p-chlorophenylthio) succinic anhydride 2-(o-methylphenylthio)succinic anhydride Z-(m-methylphenylthio) succinic anhydrideZ-(p-methylphenylthio) succinic anhydride 2-(p-nitrophenylthio) succinicanhydride Z-benzylthio succinic anhydride Z-dimethylamino succinicanhydride Z-(di-n-propylamino) succinic anhydride 2-(di-iso-propylamino) succinic anhydride Z-(di-n-butylamino) succinicanhydride 2-(di-iso-butylamino) succinic anhydride Z-(di-n-amylamino)succinic anhydride 2-(di-iso-amy1amino) succinic anhydrideZ-dihexylamino succinic anhydride 2-pyrrolidino succinic anhydrideZ-piperidino succinic anhydride 2-morpholino succinic anhydrideAnilines:

3,5-difluoroaniline 3,5-diohloroaniline 3,5-dibromaniline3,5-diiodaniline Syntheses were effected according to theabove-mentioned operational process to obtain the results as shown inthe following table:

TABLE 39 Obtained N-(3,5-dihalophenyl)-imide compound Elementaryanalysis, percent Cl Br Found Physical Yield constant (percent) 0.)

Structural formula Ex. No. Suecinamle acid CHgCHlS-?HCOOH CHIC ON(IJHICOOH CHaCHaS-CHCONH

